CORE SUMMARY/ABSTRACT Three Projects and two Cores within this P01 receive support by the now well-established Core A. Based on our two decades of experience with such oversight, we believe the notion of ?success? for the overall program depends on the P01 having an effective Administrative Core component as a central element of fiscal/regulatory coordination, human subject recruitment, and scientific guidance/external evaluation. With this belief, the four goals of Core A are as follows: 1) Coordinate the budgetary and fiscal aspects of the program. The proposed program involves direct cost disbursements to investigators of Projects 1, 2, & 3, as well as Cores A and B; hence, careful oversight represents an absolute administrative requirement. 2) Facilitate communication among investigators within the program. This aim takes a pragmatic form through Core A's implementation of a variety of functions ranging from organizing regularly scheduled meetings between program investigators to training of Project investigators by the program's Cores. 3) Coordinate, as a Program Executive Committee, ongoing feedback with regard to the directions of the individual Projects and Cores, the goals and activities of the P01, and respond to input provided by the External Advisory Board ? individuals who provide on-site visits to the University of Florida as well as teleconference based reviews ? for the purpose of maximizing both the progress and success of the program. 4) Organize the collection of human materials, generate appropriate data sets, provide statistical support to the program, assure compliance with appropriate regulatory bodies and edicts (e.g., Institutional Review Board, Health Insurance Portability and Accountability Act), and facilitate communication of program results. In addition to the aforementioned functions, the administrative staff of the program will also be responsible for communication with the NIH staff, as well as for assistance with publications and presentation of program results. It should be noted that the P01's Program Executive Committee has reviewed changing priorities and advances in the field of type 1 diabetes (T1D) and with this renewal application, organized itself to address the growing needs for: 1) identifying key processes at the intersection of ?-cell biology and anti-?-cell immunity; 2) understanding genotype/phenotype interactions in T1D that impact immune responsiveness; 3) developing improved biomarkers (immune/metabolic/genetic) reflective of key pathogenic processes; and 4) discovering methods that would impart immune modification capable of preventing/reversing T1D. Directed/collaborative activities to achieve these goals, taken together with the successful completion of these P01 studies, should continue to prove beneficial for improving our understanding of the immunological and genetic contributions critical to the pathogenesis of T1D, identifying immune/genetic markers that enhance our ability to monitor the disorder's natural history and eventually, developing immunotherapies capable of preventing or reversing the disease.